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. 2019 Sep 27;11(10):1584.
doi: 10.3390/polym11101584.

3D Bioprinting of the Sustained Drug Release Wound Dressing with Double-Crosslinked Hyaluronic-Acid-Based Hydrogels

Haopeng Si  1 , Tianlong Xing  2 , Yulong Ding  3 , Hongbo Zhang  4 , Ruixue Yin  5 , Wenjun Zhang  6   7
Affiliations

3D Bioprinting of the Sustained Drug Release Wound Dressing with Double-Crosslinked Hyaluronic-Acid-Based Hydrogels

Haopeng Si et al. Polymers (Basel). .

Abstract

Hyaluronic acid (HA)-based hydrogels are widely used in biomedical applications due to their excellent biocompatibility. HA can be Ultraviolet (UV)-crosslinked by modification with methacrylic anhydride (HA-MA) and crosslinked by modification with 3,3'-dithiobis(propionylhydrazide) (DTP) (HA-SH) via click reaction. In the study presented in this paper, a 3D-bioprinted, double-crosslinked, hyaluronic-acid-based hydrogel for wound dressing was proposed. The hydrogel was produced by mixing HA-MA and HA-SH at different weight ratios. The rheological test showed that the storage modulus (G') of the HA-SH/HA-MA hydrogel increased with the increase in the HA-MA content. The hydrogel had a high swelling ratio and a high controlled degradation rate. The in vitro degradation test showed that the hydrogel at the HA-SH/HA-MA ratio of 9:1 (S9M1) degraded by 89.91% ± 2.26% at 11 days. The rheological performance, drug release profile and the cytocompatibility of HA-SH/HA-MA hydrogels with loaded Nafcillin, which is an antibacterial drug, were evaluated. The wound dressing function of this hydrogel was evaluated by Live/Dead staining and CCK-8 assays. The foregoing results imply that the proposed HA-SH/HA-MA hydrogel has promise in wound repair applications.

Keywords: 3D bioprinting; biodegradable; double-crosslinked; hyaluronic acid; wound dressing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Scheme illustration of (a) The synthesis of 3,3′-dithiobis(propionylhydrazide) (DTP); (b) the synthesis of HA-SH; (c) the synthesis of HA-MA; (d) the schematics of double-crosslinked HA-SH/HA-MA hydrogels formation.
Figure 1
Figure 1
Scheme illustration of (a) The synthesis of 3,3′-dithiobis(propionylhydrazide) (DTP); (b) the synthesis of HA-SH; (c) the synthesis of HA-MA; (d) the schematics of double-crosslinked HA-SH/HA-MA hydrogels formation.
Figure 2
Figure 2
Preparation of bioink and 3D bioprinting of living constructs.
Figure 3
Figure 3
Hydrogel characterization. (a) 1H NMR spectra; (b) FT-IR spectra.
Figure 4
Figure 4
Rheological properties. (a) The G’ of the hydrogel without Nafcillin. (b) The G” of the hydrogel without Nafcillin. (c) The G’ of the hydrogel containing Nafcillin. (d) The G” of the hydrogel containing Nafcillin. (e) Strain Sweep Measurements of the G’ of the hydrogel without Nafcillin at a Fixed Frequency (1 Hz). (f) Strain Sweep Measurements of the G’ of the hydrogel containing Nafcillin at a Fixed Frequency (1 Hz). (g) Frequency Sweep Measurements of the G’ of hydrogels without Nafcillin. (h) Frequency Sweep of the G’ of the hydrogel containing Nafcillin.
Figure 4
Figure 4
Rheological properties. (a) The G’ of the hydrogel without Nafcillin. (b) The G” of the hydrogel without Nafcillin. (c) The G’ of the hydrogel containing Nafcillin. (d) The G” of the hydrogel containing Nafcillin. (e) Strain Sweep Measurements of the G’ of the hydrogel without Nafcillin at a Fixed Frequency (1 Hz). (f) Strain Sweep Measurements of the G’ of the hydrogel containing Nafcillin at a Fixed Frequency (1 Hz). (g) Frequency Sweep Measurements of the G’ of hydrogels without Nafcillin. (h) Frequency Sweep of the G’ of the hydrogel containing Nafcillin.
Figure 5
Figure 5
SEM images of hydrogels at different proportions (a) S3M0; (b) S0M3; (c) S1M1; (d) S2M1; (e) S3M1; (f) S4M1; (g) S5M1; (h) S9M1. The scale bars represent 100 μm.
Figure 6
Figure 6
Physical performance of hyaluronic acid (HA). (a) Swelling ratio of different samples in 3 mL PBS; (b) weight loss of all samples containing 100 U/mL hyaluronidase.
Figure 7
Figure 7
Cell culture. (a) Result of the human dermal fibroblast (HDF) Live/Dead assay. Living cells (green) and dead cells (red). The scale bars are 100 μm. (b) Cell Counting Kit-8 (CCK-8) results of HDF cells in different samples without Nafcilln. (c) CCK-8 results of HDF cells in different samples containing Nafcilln.
Figure 7
Figure 7
Cell culture. (a) Result of the human dermal fibroblast (HDF) Live/Dead assay. Living cells (green) and dead cells (red). The scale bars are 100 μm. (b) Cell Counting Kit-8 (CCK-8) results of HDF cells in different samples without Nafcilln. (c) CCK-8 results of HDF cells in different samples containing Nafcilln.
Figure 8
Figure 8
(a) Standard curve of Nafcillin in PBS; (b) In vitro release of Nafcillin in the different hydrogels in PBS at 37 °C. Data were presented as mean ± SD (n = 3).
Figure 9
Figure 9
The viability of HDF. (a) The macrofluorescence image of sample cultured for 7 days. (b) Fluorescence images of HDF in constructs after culturing for 1, 4, and 7 days. (c) Cell viability of HDF. The results showed that there was no significant difference between the two samples in terms of cell viability (p > 0.05).
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